Whether all critically ill patients need the routine administration of stress ulcer prophylaxis (SUP) has been controversial for over 20 years.Much of the evidence both for and against is of poor quality, and is pretty old.

Whether it’s that we’re ‘better’ at resuscitation now so that gastric mucosal ischaemia is less common, or whether it’s because we’re in an age of prophylaxis but I can’t remember the last time I looked after a patient with a significant stress ulcer bleed (Hb drop 2g/dL, SBP drop by 20mmmHg or 2 units of blood given).Maybe I’ve just been lucky though, as the most recent prevalence study shows that the incidence is largely unchanged from earlier series, being approximately 2%.The same paper, which surveyed 7 days of patient care from 97 European and Australasian ICUs (mainly UK and Denmark), showed that bleeding occurred early in the patient stay with a median time to bleed of 3 days.The adjusted odds ratio for 90 day mortality after a significant bleed was given as 1.7, but this was statistically non-significant (95% CI 0.68–4.28).Risk factors for bleeding from this series can essentially be summarised as the sicker the patient was the more likely they were to bleed, which goes to explain the lack of attributable mortality as in the sicker patients the bleed becomes a ‘lesser factor’. SUP does seem to have become an almost universally instituted intervention.In this US survey, 90% of patients were given SUP, with a PPI being given in 40%.The prevalence study highlighted earlier reported that by day 2, 70% of patients were receiving SUP, with this being continued to ICU discharge in 57%.PPIs were used in 55% of cases.The rise in PPI use over the years compared to Sucralfate and H2 blockers is a trend that can be traced through the literature (presumably as PPIs have got cheaper and we all want to give something ‘stronger’). The first question has to be does SUP prevent significant bleeding?Krag et al. conducted a review of the available evidence to assess the effects of SUP vs. placebo or no prophylaxis for a variety of outcomes in ICU patients.They used ‘trial sequential analysis’ which I’d never heard of but I gather is a piece of software designed to reduce the likelihood of getting positive results solely through repeated testing (if I’m wrong or someone can explain this better please leave a comment).They found no difference in all-cause mortality (the ‘all cause’ is important – if there are both benefits and risks of the intervention the net result could be no difference).Bleeding was not significantly reduced (although the section on this is incomprehensible to me), and there was no difference in pneumonia rates. The evidence on which the review was conducted however was poor.20 trials were included, 8 of which were sponsored by drug companies.19 of the trials were judged by the authors to have a high risk of bias.16 of the trials were single centre, and only 7 trials considered a mixed ICU population. Another trial of interest is that conducted by Faisy and Guerot which was not included in the above review as it was observational.This single centre study looked at rates of bleeding before and after stopping the routine administration of SUP.There was no change observed, however the SUP used was Sucralfate unless contraindicated so you may argue that there was no difference because the SUP was not effective in the first instance.It is interesting however that the incidence of clinically significant bleeding was approximately 1.5% both before and after, similar to the 2% quoted earlier. In the 27 patients who bled in the European/Australasian series, 16 (59%) were receiving SUP prior to the bleeding episode. On the basis of the Krag et al review Danish guidelines suggest that SUP should only be used in the setting of an RCT.It is probably worth highlighting that the prevalence study and the Krag paper were both conducted by the Danish SUP-ICU group.This group was represented by its founder on the guideline group and this has been declared. The closest we have to a guideline in the UK is that of the surviving sepsis campaign, which recommends SUP only when indicated.This is all well and good, however the most accepted risk factors for stress ulcer related bleeding are coagulopathy and ventilation for >48hrs.The latter ensures prophylaxis for pretty much every level 3 patient. I think there’s a definite feeling that even if SUP don’t prevent stress ulcer bleeding it is a low risk (if not low cost) intervention.Unfortunately however nothing is without risk, but the evidence for harm with SUP in general, and PPIs specifically is not exactly convincing. Whether the administration of SUP increases the risk of VAP is unclear.Pneumonia was an outcome in the Krag review, finding no difference.Prolonged ventilation is a risk factor for both stress ulcer bleeding and VAP, so there’s likely to be an association even if not causation.With this in mind, some ventilator care bundles include the administration of SUP. This really useful document summarises the evidence with regard increased risk of C-Difficile with PPIs, although the risk in critical care would be extrapolated from PPI use in the community.Having said this, C-Diff is a devastating complication, and there’s enough out there for PPIs to be listed as a risk factor, including by the Department of Health.As well as the harm caused to the patient if a PPI has been given this may just be the evidence the commissioners need to be able to apply the £10k sanction (recently reduced from £50k). There’s also an interesting concern regarding Omeprazole or Esomeprazole and a reduction in action of Clopidogrel.It was only when reading this document that I became aware of the other medications which may also reduce Clopidogrel efficacy. A decision must therefore be made with incomplete information.I think the decision as to whether to continue routine administration of SUP is different to if we were deciding to start having never done so.Stopping routine administration would require a culture change, and an acceptance of being an outlier.I do feel it would be justifiable however. To continue our current practice of starting a PPI on all ventilated patients pending review would ensure those at highest risk receive prophylaxis, which should be given early if the median time to bleed is 3 days.It would also mean exposure of many patients to a drug which could (possibly, maybe) cause harm, is unnecessary and has a financial cost. Performing a risk assessment on each patient at admission and prescribing if necessary sounds ideal, but could we reliably remove the human error and risk of omission from such a strategy?Possibly with a patient information system to prompt us? A compromise adopted by some people is to give SUP to all patients not being enterally fed.Whether food is sufficient prophylaxis is unclear.Apart from the beneficial effects of food on the mucosa, it would seem intuitive that if the upper GI tract is working it’s unlikely that there is significant ulceration (meaning that the ability to enterally feed may just be an indicator of low risk as well as being therapeutic).In the US survey mentioned earlier, 45% of intensivists agreed that enteral feeding offered sufficient protection, and 68.6% would stop when a patient is no longer nil by mouth. I’ll finish by just re-iterating that the pathophysiology of stress ulcer related bleeding is impaired perfusion, so in that respect SUP is just a sticking plaster or last ditch attempt to reverse the effects or damage already done.We must get the resuscitation right. As always, I look forward to reading your comments – what do you think we should be doing?

Pete
In the old days we used to stop prophylaxis when enteral feeding was initiated sucessfully and I don't know why or how this changed but gradually over the years it has.
I would be in favour of stopping it when EN is initiated
J

Reply

Monica Jackson

11/8/2015 01:49:16 pm

Interesting that mean time to bleed is 3 days. Given that some of the potential adverse effects of PPIs such as C.diff are associated with prolonged admissions, even if routine prophylaxis is continued maybe it should be for a limited course to cover this 'high-risk' period?